Statins affect cancer cell plasticity with distinct consequences for tumor progression and metastasis.

Statins are among the most commonly prescribed drugs, and around every fourth person above the age of 40 is on statin medication. Therefore, it is of utmost clinical importance to understand the effect of statins on cancer cell plasticity and its consequences to not only patients with cancer but also patients who are on statins. Here, we find that statins induce a partial epithelial-to-mesenchymal transition (EMT) phenotype in cancer cells of solid tumors. Using a comprehensive STRING network analysis of transcriptome, proteome, and phosphoproteome data combined with multiple mechanistic in vitro and functional in vivo analyses, we demonstrate that statins reduce cellular plasticity by enforcing a mesenchymal-like cell state that increases metastatic seeding ability on one side but reduces the formation of (secondary) tumors on the other due to heterogeneous treatment responses. Taken together, we provide a thorough mechanistic overview of the consequences of statin use for each step of cancer development, progression, and metastasis.
Competing Interests: Declaration of interests J.T.S. reports the following disclosures: Bristol-Myers Sqibb, Celgene, and Roche (research funding); AstraZeneca, Bristol-Myers Squibb, Celgene, Immunocore, Novartis, Roche, and Shire (consulting or advisory role); AstraZeneca, Aurikamed, Baxalta, Bristol Myers Squibb, Celgene, Falk Foundation, iomedico, Immunocore, Novartis, Roche, and Shire (honoraria); and minor equity in iTheranostics and Pharma15 (<3%) and member of the Board of Directors for Pharma15, all outside the submitted work. All other authors declare no competing interests.
(Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)